Growth factor-like activity of phenol red preparations in the MCF-7 breast cancer cell line

Hormonal responsiveness of the estrogen-sensitive MCF-7 human breast cancer cell line is known to vary between laboratories although the causes and implications of these variations remain unclear. Our findings lead us to conclude that the pH indicator phenol red (PHR) has growth factor-like effects in addition to its well known estrogen-like effects. To demonstrate this hypothesis, we have assessed the importance of PHR either in the absence or in the presence of the estrogens contained in the serum added to the culture medium. The basal growth rate of MCF-7 cells was significantly reduced by short-term or long-term withdrawal of PHR. The stimulatory effects of estradiol and the inhibitory effects of the antiestrogen 2-CH3,4-OH-tamoxifen (MHT) were not significantly affected by long-term withdrawal of the dye. Moreover, long-term cell maintenance without PHR alone or in complete estrogen-depleted medium did not change their basal steroid receptor content. The molecular structure of the estrogen receptor which is usually modified under estrogenic stimulation remained identical whether or not the cells were maintained in the presence of the dye. Maintaining cells without the dye in the presence of serum estrogens led to the death of the cell line after 50 transfers. Lastly, addition of PHR had clearcut growth stimulatory effects on the hormono-independent cell line Evsa-T.